The parasite Plasmodium falciparum causes an acute form of malaria. The disease is endemic in much of equatorial Africa, Southeast Asia, and Central and South America. Insecticide spraying to kill the mosquito vector as well as distribution of antimalarial drugs to residents have failed to eliminate malaria in these areas. Control of the parasite is now plausible through application of hybridoma and recombinant DNA technologies in the production of an antimalarial vaccine. The invasive merozoite stage of the parasite contains organelles called rhoptries. The rhoptries appear shortly before release of the merozoite from one infected erythrocyte and disappear again shortly after invasion of a new erythrocyte. Monoclonal antibodies which bind antigen(s) of the rhoptries are capable of inhibiting parasite invasion and/or growth in an in vitro assay and, in a rodent model system, are found to protect mice from parasite challenge. The aim of the proposed research is to identify and sequence genes which encode rhoptry-specific proteins and to determine the relationship of the multiple polypeptides currently thought to be associated with this organelle. These results should ultimately indicate: what portions of the molecule(s) might be suitable in an antimalarial vaccine, how this organism controls development of this stage-specific organelle, and precisely what function the rhoptries play in parasite development, homeostasis, and invasion.